Parenteral solution container



Dec- 15, 1964 R. w. BARTON ETAL 3,161,310

PARENTERAL SOLUTION 1 CONTAINER 2 Sheets-Sheet 1 Filed Oct. 14, 1960 mum Dec 15, 1964 R. w. BARTON ETAL 3,161,310

PARENTERAL SOLUTION CONTAINER Filed Oct. 14. 1960 2 Sheets-Sheet 2 iniited? States Patent ce 33362310? PARENTERAL SOLUFHNJ (SNTAlNER Raymond W. Barton',- Evansvlle, Ind., Hermannv Heclrel,

xford, Qhio, andlaul Prielrettand Edward G. Swenson, Evansville, Ind., assignors, by inesne assignments,

t@ Don Baxter, Ina., Glendale, Calif., a corporation of Nevada K y Filed st. 14, 1960, Ser. N 62,585 4 Claims'. (Si. 21S-Alf) This invention is concerned with a formed plastic parenteral solution container, a method of filling and sterilizing such containersv and related apparatus.

parenteralA solutions, designed for infusion or intravenous feeding of patients have commonly been packaged in glass bottles of varying sizes'. Glass bottles are quite heavy, relatively expensive, subject to breakage when mishandled and provide a' disposal problem for the hospital, as they are not consumed by incineration'.

Efforts have been made to provide plastic solution containers of synthetic plastic materials. Most of the Work in-this field has been concentrated on collapsible bags of plastic film materials, but this type of container presents several serious problems. plastic bag is not self-supporting and if, as frequently happens, the administration of a solution must be interrupted to switch to blood, the administration apparatus is disconnected from the solution container andthe remaining solution runs out. The lack of sufficient rigidity to be self-supporting makes lling extremely diicult; and in practice the containers are formed and filled simultaneously. Automatic machines for performing these operations are relatively slow as compared with bottle-filling machines, adding to the manufacturing costs. In addition, such containers must bellieatsealed with liquid in them. Itl is difficult to malre seals ofy this character with consistent quality in a production operation.

Another problem with plastic lm containers' is that water vapor escapes: through the container walls. If the containers are stored for aperiod of time even as short assix to nineV months, the concentrationr of the contents maybe seriously increased.

A principal objecty of thisv inventionis the provision of a molded plastic bottle having adequate strength and sufficient clarity to permit visual inspection of the contents and having a temperature characteristic allowing the use ofd heat sterilization, asin an autoclave.

One feature of the invention is the provisionJ of acon- Vtainerr particularly designedl for parenteral solutions, in'- cluding a bottle of blow-molded, intermediate density .polyethylene plastic material; and preferably the bottle, which ispartially deformable but not` completely col-- lapsible, hasa first portionV provided with a rupturable diaphragm for connection with an' ad'minist'rationv set and another portionl provided with ar re`sealable diaphragm for insertionV ofI anv air inlet device. Another feature of the invention is that the solution bottle i's substantially completely filled withV parenteral solution and has-'a minimum-air spacetherein- As will' appear,y the substantially complete lill reduces the possibility of distortion of the container duringsterilization;

A furtherfeature isftliat the" container 'has apanel of transparent tape adhesively secured'to a wall' thereof to improve *theftransmission oflight therethrough,v permitting visual-inspectionfof the contents.

Stillanother featureoffthe' invention" is that the bottle has arecessedbottom'- portion' with"l a centrallyA located depending tab, havingan open space therearound between the tab andthe peripheral portion of the bottle bottom. A` suspensionmeans for the bottle"is-attachedfto 'the tab andrdisposable within the open spacefsurrounding the tab when` the bottle restson the'surface. A further feature 35,161,3r0f` Patented Dec. 15, 1964 isi-that the suspension rrieansy forthe bottle'- comprises a length of plastic tubing having its' endsrvtelescoped and sealed together.

Yet another feature of the invention is the provision of a bottle of molded plastic material having an indented area formed in the wall' thereof with a pad of puncturable resealable material located in the indented area and a covering of a tapeelike material overlying the pad and adhered to the adjacent container wall; `and more specifically, first and second indented areas are formed adjacent each other withA the end of the tape-like material extending partially over the second indented area to facilitate the removal of the tape.

And a further feature of the invention is the method of packaging a solution in a plastic container which cornprises providing the container with a support, filling the container and sterilizing the supported' container and contents at a temperaturev above the softening temperature of the plastic material. Another feature of the packaging method is that the container is substantially completely filled, minimizing the air space therein and reducing the possibility of distortion or deformation of thev container during autoclavi-ng.

A` further feature of the invention isV the method of applying atape panelA tothe wall of the container which includes the step of warming the container to an elevated temperature and applying the tape panel at the elevated temperature, permitting the adhesive to ll the irregularities of the container surface. Still: another feature is the step of wetting the' surface of the container with an adhesive solvent before applying the tape, to cause the adhesive to conform intimately Withthe irregularities ofthe surface.

And' a further feature of the invention is the provision of an a-ir inlet filter device for a-` plasticparenteral solution-containerV in which means are provided for preventing the solution wetting the filter material. More specifically, the filter device includes an elongated body with a cannula at one end for insertion into the container and a massl of lilter material at the other end, remote from the cannula. In an alternative structure, the air inlet device includes a manually operable' valve member between the cannula and the lter material;

Further features and advantages of the invention will be' apparent fromv thefollowing specification andl from the drawings in Which:

FIGURE l is an elevational- View of a container embodying the' invention;

FIGUREZ is an elevationalview of the container in use,y with an infusion setv connected thereto;-

FIGURE 3 is anl enlarged fragmentary sectional view of the lower portion ofthe container, illustratingv the supporting arrangement;

FIGURE 4 is'anenlarged fregrnen-tary sectional view taken generally along-the line 4;-4 of' FIGURE 6, illustrating the air intake resealabrlepad and its mounting;

FIGURE 5 is `an enlarged fragmentary sectionalview of the neck of the container and the closure therefor;

FIGURE 6 is a fragmentary elevational view of the resealable entry pad;

FIGURES7-9 are diagrammatic views illustrating steps of the lling and sterilizing method according to the invention; A Y

FIGURE: l0 is an elevational View', partially in section, ofpan air inlet filter device for use'witli'y the plastic container; l

FIGURE llfis'a-fraghint'ary view, partially in section, of'a modified air'lilter; and" FIGURE' 1-2 is a sectional'vievv` of another modified air lter.

Several ybasic requirements for' parenteral 'solution containers must' beA met in adapting a plastic material'for space for packaging and storage. ztainer, utilizing the medium density polyethylene material Y Y 3,161,310Y

filling operation is carried on` under sterile conditions,

which is generally so diiiicult that .it is economically unfeasible. Furthermore, the most practical sterilization One of the most important requirements reprocedure for parenteral products is to heat the filled containers to a temperature in excess ofy 220 F., and

maintain it at the elevated vtemperature for a period, as

of the order `of one-half hour. Such an operation is 4 Air is admitted to the container through a filter 32 suitably connected vwith the container, as will appear.

The suspension arrangement for the container is best seen in FIGURE 3.r The bottom portion 34 of container 20 is formed inwardly defining a recess surrounded by a peripheral bottom portion 3S.` Centrally located in the recess is a diagonally extending depending tab 36, provided with an aperature 36athrough which the suspension member 26 extends. A plurality of feet 37 are formed onvthe bottom of the peripheral portion of 35 of the container and'hold the peripheral portion spaced Vfrom a supporting surface 38 on which the container may normally carried on in an autoclave and is often referred v' to as autoclaving Accordingly, it is necessary that the plastic material used besuch that it will not fail at this elevated temperature. This in itself is not too difiicult to attain with the presently available plastics, such as the high density polyethylenes'. However, another important requirement is thatV the container be such that the contents can be visually. inspected before use, with sufficient clarity to permit observation of small-particles, such as may be caused by'formation of a precipitate in the solution. Hence, Ithe material must Ypermit relatively undiffused passage yoflightthrough the container walls.

In additiomthe container must have sufficient strength to withstand hydrostatic shocks 'incurred during handling and shipment and must not be subject to stress'failures during aging, as the products may be stored for-sometime before use.

A further requirement is that'the plastic material shall stand inan upright position. lThe downward extent of depending tab 36 is such that its lower extremity is spaced above the support-ing surface.` The suspension member 26 fis received within the recess surrounding .tab 36 and may extend Voutwardly between the peripheralV bottom portionl 35 ofthe container, between Ythe feet 37, with- I lout interfering with the stability of the container.

.scoped and sealed together.

. on by an outside'force, and, when the container is innot permit contamination of the contents over a period of time, either directly from the plastic itself, or by the slow diffusion orl migration of air-borne contaminants through the container Wall.

As pointed out above, high density-polyethylenesV provide the heat resistance required for autoclaving. However, they do not have suii'icientclarity to permit visual Vinspection of thev contents of the container.v Certain polyvinyl plastics have the heat'resistance and clarity which are required, but have been found to introduce contamination aftera period yof storage; and are relatively ex- Turning now to the drawings, a container 20V embody- Y ing the invention is illustrated in FIGURE 1.` Container 20 is bottle-like in configuration, and has an opening defined by a neck 21 closed by a cap 22 which is in Aturn, covered by a plastic film seal 23. 'The container or bottle 20 hasfa generally squareV cross-sectionV74 with rounded corners for maximum strength with greatest economy of In acne-liter size conspecified above, the thickness 4of the side panels of the container, which are the thinnestportion of the bottle,

is of the order of 0.015 inch. This is the minimum thickness obtainable with present molding techniques to achieve a bottle with sufficient strength,` particularly in thebottom portion thereof, to'withstandthe stresses of handling. A

label 24 fixed tothe side wall ofthe container 20 carries termined whether the" container is upright or inverted.

FIGUREZ illustrates the container 20 as .it is used in dispensing the solution. The container is hung in an inverted, may readily be attached to a hanger. The suppor-t 26 is preferablyassembled by threading a length-Of the plastic tubing material through the opening 36a in the tab, dipping onev end in a' solvent for the plastic and then telescoping/ the ends of the tubing. When the solvent evaporates, the ends are firmly welded together.

The neck 21 of container 20 is providedrwith a plug or yiitment 40 whichserves as a closure for the container yand also .provides'for the 'connection thereto of a suitable administration apparatus. The plug is preferably of polyethylene'material, and has an outwardly extending v rim 41 which seats on the surfaceof dient-eh21 of the container, properly. positioning the plug in Vthe neck. After insertion, the plug is heat sealed in place, bonding the interface between the inner surface of the neck.V and the. outer wall surface of the plug. The Vplug is centrally recessed and is provided with an upstanding central tub ular portion-t2 closed at its inner. end by an integral,

rupturable diaphragm 43. The innerfdiameter of tubular portion 42 is'such that it seals with the surface of the spike or cannula 30 of the administration set upon in# sertion thereof to a depth less than that lsufficient to 'cause the pointed end portion to rupture the diaphragm. This prevents leakage of the contents during the attachment ofthe administration set.

Inasmuch as the container 20 is onlyy slightly deform- -ableor collapsible, it is necessary to provide for the entry of Vair to permit the contents to flow out through the ad-l ministration set. .Y A side wall of the container, adjacent .the bottom thereof, isprovided with a pair` of indented'or depressed areas 46 and 47, with the area-47 being adjacent to and directly below the area 46. A disc of resealing rubbery material, asl ai gum rubber, is aixed to the indented arca 46 and provides for the insertion of the spike ofan'l air inlet and filter device. The resealing disc 48 preferably has laminatedthereto a layerof double-sided,

pressure-sensitive,'tape 49' having afpolyvinyl ether ad-y hesive'which has been found to adhere satisfactorily to the plastic containerfwall.VV By -doublesided is meant a ltape whichhasf a pressure-sensitive adhesive on both survertedposition by a supporting element or` suspension jmember. 26 from 'a suitable carrier 27, as a hook. VAn

administration set 28 has a part 29 with a cannulafor spike 30 which is inserted through an outlet in neck 21 ofthe container, for conducting the solution toapatient.

faces thereof.; The tape 49 then' serves as the ymeans for securing the disc'48 to the .container wall. The sterility of the disc 48 is maintained during handling'and storage: by a .covering of tape 5t) :havingfa layer of adhesive on one side, which overlies the disc and is sealed to the wall?.

of the container around the disc and indented area 46..

AAn end vportion 50a of the tapeA strip'extends partially over' the lower indented area 47 providing readily manually engageable surface for grasping the tape to remove it.

The procedure followed in filling and sterilizing the container 20 is particularly important in permitting the practical utilization of polyethylene plastic material as the container. The preferred sequence of steps in the filling and the sterilizing operation are illustrated in FIG- URES 7-9. In FIGURE 7, the plastic container 20 is shown received in a supporting sleeve or canister 54 which conforms generally with the shape of the empty container and holds it during the filling and sterilizing operation. The container 26. preferably has a sliding fit inside the supporting canister 54. Supporting canister 54 is preferably of a reasonably rigid construction, as of sheet aluminum, and is provided with feet 55 which support the bottom in spaced relation from a supporting surface 56 to permit circulation of steam about the canister. A slot extends across the bottom of the canister to allow steam to enter and reach. container 2t). The slot is so located that diagonally extending tab- 36 cannot enter it.

The empty container 20 is placed in the canister 54 and then filled', as from a suitable filling head 57. The parenteral solution is preferably delivered to container 20 at an elevated temperature, as of the order of 140-l90 F. Thisservestwo functions: first, it reduces the quantity of dissolved gases. in. the parenteral liquid which might be riven off' and stretch. they bottle during autoclaving; and second, it reduces the time required to bring the filled containers to sterilization temperature in the. autoclave, The container 2.0. isY as. nearly completely filled as'possible, minimizing the quantity of air trapped therein. This reduces the danger of distortion of the container by high pressure: gasy when. the plastic walls .are softened during autoclaving. The filled container isl provided with closure plug 4f) whichissealedin place.

A quantity. of the filled. and supported containers 20 are then placed in an. autoclave. 58', FIGURE 8, in which they are held on spaced shelves59. Steam isV introduced into the autoclave, as. through, valve 60,. at a temperature of the order of 23.0 E.. for the medium density polyethylene material describedv above. This condition is maintained for a. period. of the order of thirty. minutesy to insure complete sterilization of they product. The ternperature at which autoclaving is carried on requires a pressure of theorder ofy 8--110 pounds per squareV inch. The sterilization temperature is in: the range in which the plastic material softens. and is` readily deformable. The support provided by canister 54 and the absence of an excessive. volume of air in the container reduce this problem.

Following the autoclaving period', the steam within the autoclave 58 is vented, and cooling water, as at a temperature of 190 F. introduced, as through valve 6l. An over-riding air pressure of the order of 12-16 pounds per square inch is introduced into the autoclave through valve 62 before or concurrently with the venting of the steam. After the bottles are suitably cooled, they are removed from the autoclave 58, the upper surfaces of the plug sterilized and cap 22 applied.

The label 24 which carries identifying indica and graduations indicating the quantity of liquid in the container, serve further purposes. Molding procedures make it desirable to have a roughened surface on the container to facilitate removal from the mold. This surface irregularity diffuses light passing therethrough rendering impossible visual observation yand inspection of the contents with the :accuracy or clarity necessary. However, it has been found that if a layer of clear plastic material is adhered to the container surface, the clarity of the container is markedly increased. It is believed that the penetration of the adhesive on the tape into the irregularities of the surface of the blow-molded container reduces the diffraction or dispersion of light passing therethrough, and permits the required visual inspection. It is preferable that adhesive-coated panels be applied to opposite walls of the container, for maximum light transmission and clarity. The adhesive on the tape must be of sufficient thickness and have adequate flow characteristics to penetrate into the surface irregularities of the plastic material. The results are improved by applying the tape panels when the containers are warm or at elevated temperatures, permitting the adhesive to fiow into the irregularities of the surface more freely; or by wetting the surface with an adhesive solvent, yas alcohol or an alcohol-glycerine mixture, prior to the application of the panel. Transparent cellophane tape marketed by Minnesota Mining and Manufacturing Company under the trademark Scotch has been found satisfactory.

The indicia-bearing tape panels have the further beneficial effect of increasing the effective strength of the container, reducing the possibility of rupture during handling.

The air entry patch 48 and its covering tape strip 50 are preferably applied to the wall of the container prior to filling. The adhesive bondy between the patch and the bottle wall is improved by the pressure applied thereto as a result of the weight of the container contents, while the container is confined within the sleeve k54, and at the same time heated to a point where the adhesive is intimately bonded with both the patch and the container wall.

For proper utilization of the resilient plastic parenteral container 20, a specially designed air inlet-filter device is desirable. When the spike of the air inlet is forced through the wall of the container, it requires the application of a substantial pressure on the container. The resulting. deformation of the container places the contents under pressure and may force some of the contents into the air inlet device wetting the filtering medium and rendering it relatively unfit for use.

A novel air inlet and filter device' construction is illustrated. in FIGURE 10. The filter body 65 is elongated, and has a sharpened connula or spike 66 at one end thereof, for insertion through` the wall of the container. The body 65 is elongated in a direction generally coaxially with the spike 66 and is provided at its outer end, remote from the spike, with a mass 67 of a suitable filtering material as sterile cotton. The spacing` between the' spike and filter material is preferably of the order of one inch. The outer end of the elongated filter body has a pair of air inlet holes 68' formed therein, and suitably closed prior to use as by a cap 69. If desired, a strip of adhesivevcoated tape 70 may be affixed to the outer end of shoulder body 65, overlying the air inlet holes 68'. The tape may be lifted up to permit air to flow into' the holes and replaced at will,. to control the entry of air into the container, and thus the administration of the parenteral solution.

A modified construction is shown in FIGURE 11 where the air inlet opening 72 is formed in the end wall of the filter body 73, immediately adjacent the filter material 74. A removable and replaceable rubber cap 75 is fitted over the end of the filter body to close the opening 72.

Still a further modification of the air inlet and filter device is illustrated in FIGURE 12. Here the filter body 78 has a cannula or spike portion 79 extending from the end wall thereof and filter material 80 is carried in the cup-like filter body. A valve member 81 is provided in the air inlet body and seats against the end wall from which the cannula projects. The valve is provided with a valve stem 82 having a portion 82a which extends into the bore 79a of the spike 79 serving as a guide for the movement of valve 81, The second portion 82b of the valve stem extends outwardly through the filter material Sti to permit manipulation of the valve. With the air filter and inlet of FIGURE 12, the spike is inserted through the wall of the container 20 with the valve 81 in closed position. This prevents any of the contents of the container from fiowing outwardly and wetting the filter material. The valve 81 may then be opened by V7 pulling outwardly on valve stern' portion 82b,-admitting air when it is desired to administer the solution. y

While we have shown and described certain embodiments of our invention, it i'sto be understood that it is capable oi Vmany modiications. Changes, therefore, in

disclosed in the appended claims.

We claim:

l. A container of solution suitable for intravenousrad-y 1ninistration, comprising: a bottle being flexible but being the construction and arrangement may be made without f departing from the spirit and scope'of the invention Vas 'f ieast one of said scales depending upon the covering of tape-like material overlying said pad and adhered to the wall of said container surrounding said rst,

indented area, said tape having an end portion extending `partially over said second indented area.

being partially, deformable but being sufficiently rigid to maintain its shape and to stand upright when iilled with a liquid, said bottle havingan indented area formedin a side wall thereof; a padv of puncturable resealable material llocated in and` substantially illing said indented area, said pad being on the outside'pf said rigid bottle;

a double-faced,` polyvinyl ether adhesive adhered to one tion in the bottle, said bottle being relatively iiexible and being retained substantially rigid by said solution contained therein and maintained uprightby said solution; and an elongated panel substantially the length of said bottle and secured tothe outer surface thereof over a portion of said irregularities, said panel comprising a transparent tape having at least one indicia scale extending along .the length of ,said tape and calibrated to ascertain the amount of'solution in said bottle, said tape including a'transparent adhesive filling the irregularities of f 4. A sealed container as claimed in claim 3 (including a second indicia scale similarrto said lirst mentioned in-A dicia scale and disposed in an opposite direction with respect to said first4 mentionedindicia-scale whereby the v level of said solution can ,be readily compared with at "inverted attitudeofthe bottle.

VReferences Cited in the iilefof this patent UNTED STATES vPATENTS l 82,028 'Percival Sept. 8, 1868 ,72,065,012 Muleford Dec. 22, 1936 2,128,652 'Kratz et al. Aug. 30, 1938 2,294,574v Ravenscroft et al Sept. 1, 1942 2,362,980 Ball Nov.,21, 1944 2,380,696, James July 31, 1945 2,438,149 Cutter et al Mar. 23, 1948 2,507,684 Smith May 16, 1950 2,520,124 'Chaney Aug.v 29, 1950 2,559,284 Dickschat July 3, 1951 2,638,430 Mann May 12, 1953 2,660,513 Ball Nov. 24, 1953 2,699,103 Stasikewich Ian. y11, 1955 .l 2,704,075 l -Cherkin Mar. 15, 1955 2,787,268 Greenspan Apr. 2, 1957 2,808,829 Butler Oct. 8, 1957 2,825,521" VvNesset Mar.`4, 1958 2,835,623 Vincent et al. May 20, 1958 2,837,245 Grebowiec June 3,1958 2,845,728 `Huber Aug. 5, 1958 'l 2,886,035' Loutz May 12, 1959 2,906,423 Sandhage Sept. 29, 1959 V2,936,920 Wallace May 17, 1960 3,041,775 Brown et al.v July 3,V 1962 3,064,652` Corcoran etal. Nov. 20, 1962 FOREIGN PATENTS 190,566 Great Britain Dec. 28, 1922 VOTHER REFERENCES' Precocious Plastic, article in ModernI Plastics, volume V25, pp. 73-80, February l948.` y

Heat Sterilization in Plastics, article in Modern Pack- 5 aging, pp. 165-167, september 1957.y

upright or 

2. A CONTAINER OF SOLUTION SUITABLE FOR INTRAVENOUS ADMINSTRATION, COMPRISING: A POLYETHYLENE PLASTIC BOTTLE BEING PARTIALLY DEFORMABLE BUT BEING SUFFICIENTLY RIGID TO MAINTAIN ITS SHAPE AND TO STAND UPRIGHT WHEN FILLED WITH A LIQUID, SAID BOTTLE HAVING AN INDENTED AREA FORMED IN A SIDE WALL THEREOF; A PAD OF PUNCTURABLE RESEALABLE MATERIAL LOCATED IN AND SUBSTANTIALLY FILLING SAID INDENTED AREA, SAID PAD BEING ON THE OUTSIDE OF SAID RIGID BOTTLE; A DOUBLE-FACED, POLYVINYL ETHER ADHESIVE ADHERE TO ONE SURFACE OF SAID PAD AND TO THE WALL OF SAID BOTTLE WITHIN SAID INDENTED AREA; AND A COVERING OF TAPE-LIKE MATERIAL OVERLYING SAID PAD AND ADHERED TO THE SIDE WALL ADJACENT SAID INDENTED AREA, SAID PAD REMAINING ATTACHED TO SAID BOTTLE WALL AND BEING EXPOSED UPON REMOVAL OF SAID TAPELIKE COVERING. 